The role of Nocardia seriolae-induced autophagy in the development of chronic inflammation in the liver and the formation of granulomas in largemouth bass (Micropterus salmoides).

Nocardia seriolae can lead to the development of granulomatous lesions in infected fish, but the exact mechanism responsible for this effect is not fully understood. Here, we assessed the impact of autophagy on granuloma formation through pathological observations and analysis of infection characteristics in N. seriolae -infected largemouth bass (Micropterus salmoides). In our model of chronic inflammatory granulomas, we observed that the expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in infected fish may be regulated by autophagy during granuloma formation. Through the infection experiments in vivo , we measured the expression of autophagy-related genes and autophagic processes. The results showed that N. seriolae induced autophagy and possibly enhanced the fusion of autophagosomes with lysosomes. Examination of immunofluorescence and ultrastructure of infected head kidney primary macrophages and measurement of the expression of pro-inflammatory cytokines revealed that autophagy in macrophages promoted the fusion of autophagosomes and lysosomes while inhibiting the expression of IL-1β and TNF-α. Structural biology analysis of microtubule-associated protein 1 A/1B-light chain 3 (LC3) demonstrated that structure basis and function of autophagy may highly conserved from largemouth bass to humans. In conclusion, our findings suggest that autophagy may play a key role in regulating the formation of chronic inflammatory granulomas, which provides a novel scientific foundation for understanding the pathogenic mechanism of N. seriolae. • Infection of Micropterus salmoides with Nocardia seriolae induces autophagy. • Autophagy inhibits the expression of pro-inflammatory cytokines in primary head kidney macrophages of Micropterus salmoides. • Autophagy may be one of the key factors regulating chronic inflammatory granuloma in the liver of Micropterus salmoides. [ABSTRACT FROM AUTHOR]